Investigating the Features of Protein-Protein Interactions to Enable the Rational Engineering of Binding Proteins and their Interfaces

ABSTRACT

AlphaFold was published in 2021 and seemingly overnight effectively solved the protein folding problem, which had been an open challenge for decades. Since then, AI and ML methods have transformed the fields of (computational) protein science and engineering, culminating in the Nobel Prize being awarded in 2024 to the inventors of AlphaFold and the pioneer in this area. Thanks to these developments, it is now possible to start answering meaningful engineering questions about proteins, like what features should a protein have to best accomplish a particular task?

The PROTEIN PANT(z) Lab has been investigating interfaces between proteins to identify what features are important to protein binding with an eye towards enabling the rational design of binding proteins. Through investigating the stabilization of pairs of interacting residues in protein interfaces, we have identified novel features that appear to be critical to protein binding. In turn, these features have allowed us to develop state-of-the-art methods for predicting the changes in binding energies of protein mutations and classifying which computational models of protein complexes work when experimentally tested.

BIOGRAPHY

Robert Pantazes joined the Department of Chemical Engineering at Auburn University in 2016, where he leads the “Pantazes Research Organization for Theoretical and Experimental INvestigations of Proteins and Novel Therapeutics (with zest!)” group (a.k.a. the PROTEIN PANT(z) Lab). They focus on developing and experimentally verifying computational methods for designing and engineering proteins, with a current focus on binding proteins for therapeutic and sensing applications. He completed his PhD at Penn State University in 2014 under the supervision of Costas Maranas, where he developed computational methods for designing antibodies. From 2014 to 2016, he did an experimental postdoc at the University of California – Santa Barbara, where he worked with Patrick Daugherty on identifying biomarkers for autoimmune diseases.